Role of viruses in gastrointestinal cancer

Abstract

Gastrointestinal cancers are a global public health problem, which represent a vast majority of all cancer‐caused deaths in both men and women. On the other hand, viral pathogens have been long implicated as etiological factors in the onset of certain human cancers, including gastrointestinal tumors. In this regard, Human Papilloma Virus (HPV), Epstein‐Barr Virus (EBV), and John Cunningham Virus (JCV) have been more strongly suggested to be involved in gastrointestinal carcinogenesis; so that, the association of HPV with oropharyngeal and anal cancers and also the association of EBV with gastric cancer have been etiologically confirmed by epidemiological and experimental investigations. Although, the association of other viruses is less evident, but may rely on co‐factors for their oncogenic roles. Therefore, to improve the prevention and treatment of these classes of cancer, their association with viral agents as potential risk factors should be investigated with care. In this respect, the present review has focused on the existing literature on the subject of viral involvement in gastrointestinal tumorgenesis, by covering and discussing various gastrointestinal cancers, corresponding viral agents and their oncogenic aspects and then summarizing evidences either supporting or rejecting a causal role of these pathogens in gastrointestinal malignancies.

Viruses as key modulators of the TGF‐β pathway; a double‐edged sword involved in cancer

“…62 In these tumors, EBV establishes latent infections, expressing only a subset of viral genes, allowing the virus to affect cellular signaling contributing to oncogenesis. 63 EBV may interfere with TGF-β signaling to promote tumorigenesis ( Figure 5).…”

“…CMV is a Herpesvirus associated with several tumors, such as colon, breast, and prostate cancers, acting as an oncomodulator by which enhance tumor growth through interfering with cell signaling in an established malignancy. 63 CMV also associates with poor graft outcome in renal disorders, and can result in miscarriage, stillbirth, and retardation of fetal growth in pregnancy. 85,86 Investigations showed the expression of TGF-β in a variety of cells and tissues during CMV infection; brain samples of AIDS patients who had CMV encephalitis were indicated to have viral inclusions co-localized with TGF-β protein in cells with astrocyte-specific glial filaments.…”

DNA methyltransferases in virus‐associated cancers

“…96 Helmbold JCV is frequently detected in colorectal cancers (CRCs), 98 and its contribution in CRC onset has been addressed in many studies. 99 Goel et al showed that JCV TAg is linked to promoter methylation resulting in CpG island methylator phenotype (CIMP) in CRCs. 100 CIMP is noted as one of the mechanisms that elevates gene expression diversity in colon cancers.…”

Infection‐associated epigenetic alterations in gastric cancer: New insight in cancer therapy

“…JC virus is involved in gastric carcinogenesis through genetic and epigenetic alterations (Mirzaei, Goudarzi, Eslami, & Faghihloo, 2017).…”

“…Several studies indicated that JCV T-Ag plays a significant role in JCV oncogenesis (Mirzaei et al, 2017;Vilkin & Niv, 2011 (Ksiaa et al, 2010;. JCV can also induce aberrant promoter methylation in other genes such as CACNA1G, CRABP1, NEUROG1, RUNX3, and SOCS1 in gastric adenocarcinoma (Yamaoka et al, 2009).…”